Monoclonal Antibodies

A Review of Pertinent Drug Information for SARS-CoV-2

Jessica Ortwine, PharmD, BCIDP Clinical Pharmacy Specialist, Parkland Health & Hospital System [email protected] @jkortwine

Data as of February 25, 2021 Adaptive Immunity • Active immunity: seroconversion occurs within 1-3 weeks of COVID-19 symptom onset

• Passive immunity: direct administration of monoclonal antibodies (mAb) or convalescent plasma • Benefit of mAb: target specific viral epitopes and domains, mass produced, administered in a specified quantity, no reliance on donors

Zhao J, et al. Clin Infect Dis. 2020;71:2027-34. https://doi.org/10.1093/cid/ciaa344 Mechanism of Action • Monoclonal antibodies prevent and possibly treat COVID-19 via multiple effector functions • Antibody-mediated neutralization of pathogen • Antibody-dependent cellular cytotoxicity • Antibody-dependent cellular phagocytosis

Lu LL, et al. Nat Rev Immunol. 2018;18:46-61. https://doi.org/10.1038/nri.2017.106 Mechanism of Action • Spike (S) protein essential for: • Viral attachment to host receptor (S1) • Virus-cell fusion (S2)

• Monoclonal antibodies (mAbs) bind to receptor binding domain (RBD) of S protein • Block viral entry into host cells

Jiang S, et al. Trends Immunol. 2020;41:355-9. https://doi.org/10.1016/j.it.2020.03.007 Eli Lilly – Bamlanivimab Alternate Names: LY3819253 LY-CoV555 Bamlanivimab – In vitro Activity • Greater neutralization potency than other RBD-binding, ACE2- Neutralization Potency blocking antibody finalists, despite similar binding affinities

• Ability to bind to RBD in both “up” and “down” conformations may account for increased neutralization activity

Jones BE, et al. bioRxiv [Preprint]. 2020. https://doi.org/10.1101/2020.09.30.318972 In vivo Animal Data Rhesus Macaque

Prophylaxis Methods Antibody administered intravenously 1 day prior to viral challenge Viral Inoculum 1.1 x 105 PFU 1 mg/kg (N=4) 2.5 mg/kg (N=4) Antibody Doses 15 mg/kg (N=3) 50 mg/kg (N=3) Control (N=4) Lower respiratory tract (LRT): Nasal swab, throat swab Sample Types Upper respiratory tract (URT): BAL, lung tissue Outcomes Change in viral load (gRNA and sgRNA)

Jones BE, et al. bioRxiv [Preprint]. 2020. https://doi.org/10.1101/2020.09.30.318972 In vivo Animal Data Rhesus Macaque Key Findings • Reduced viral concentrations and replication on day 1 in all BAL and most LRT samples • Viral replication undetectable in all locations by day 3 at most doses

Jones BE, et al. bioRxiv [Preprint]. 2020. https://doi.org/10.1101/2020.09.30.318972 Eli Lilly – Etesevimab Alternate Names: JS016 LY3832479 LY-CoV016 Etesevimab – In vitro Activity • Two potential monoclonal antibodies initially identified from convalescing patient • Similar ability to block binding of SARS-CoV-2 RBD to ACE2 receptor • Bind to overlapping epitopes • Lower 50% neutralization dose against infected cells for CB6

Shi R, et al. Nature. 2020;584:120-4. https://doi.org/10.1038/s41586-020-2381-y In vivo Animal Data Rhesus Macaque

Prophylaxis Treatment Antibody administered 1 day prior Antibody administered on day 1 and day Methods to viral challenge 3 post-viral challenge 5 Viral Inoculum 1.0 x 10 TCID50 50 mg/kg (N=3/group) Antibody Dose Placebo (N=3) Sample Type Throat swabs Change in viral load (RNA) Outcomes Pathological lung damage

Shi R, et al. Nature. 2020;584:120-4. https://doi.org/10.1038/s41586-020-2381-y In vivo Animal Data Rhesus Macaque Key Findings • Low levels of virus detectable among animals receiving prophylactic doses • Treatment doses resulted in reduced viral loads by day 2 compared to placebo • Reduced infection-related lung damage in both prophylaxed and treated animals

Shi R, et al. Nature. 2020;584:120-4. https://doi.org/10.1038/s41586-020-2381-y Clinical Trials

NCT Number Patient Population Treatment Groups Status LY-CoV555 NCT04427501 Recruiting – some results Treatment of outpatients with mild to moderate COVID-19 illness LY-CoV555 + LY-CoV016 BLAZE-1 available Placebo LY-CoV555 NCT04497987 Prevention (and treatment) of COVID-19 illness in skilled nursing and Recruiting – press release LY-CoV555 + LY-CoV016 (treatment arm only) BLAZE-2 assisted living facility residents and staff data available Placebo LY-CoV555 NCT04634409 LY-CoV555 + LY-CoV016 Recruiting – press release Treatment of outpatients with mild to moderate COVID-19 illness BLAZE-4 LY-CoV555 + VIR-7831 data available Placebo NCT04701658 Treatment of outpatients with mild-to-moderate COVID-19 at high risk LY-CoV555 Not yet recruiting BLAZE-5 for progressing to severe illness Standard of care NCT04518410 LY-CoV555 Treatment of outpatients with mild to moderate COVID-19 illness Recruiting ACTIV-2 Placebo NCT04501978 LY-CoV555 Treatment of hospitalized patients with COVID-19 illness Halted – results available ACTIV-3 Placebo

Source: https://clinicaltrials.gov Ambulatory Treatment BLAZE-1

Study Design Treatment Groups Outcomes • Phase 2, double-blind RCT • Part A: LY-CoV555 • Primary: • Non-hospitalized adults monotherapy • Change from baseline viral • 7000 mg IV x 1 load at day 11 (± 4 days) • ≥ 1 mild/moderate COVID- • 2800 mg IV x 1 from positive results 19 symptom • 700 mg IV x 1 • Secondary: • 1st positive SARS-CoV-2 • Placebo • Safety test ≤ 72 hours from start • Part B & C: LY-CoV555 + • Symptom burden of infusion LY-CoV016 combination • COVID-19 related hospitalization, ED visit, or • High risk for complications • 2800 mg/2800 mg IV x 1 (Part C only) death at day 29 • Placebo • Viral clearance

Chen P, et al. N Engl J Med. 2021;384(3):229-37. https://doi.org/10.1056/NEJMoa2029849 Gottlieb RL, et al. JAMA. 2021. [Epub ahead of print]. https://doi.org/10.1001/jama.2021.0202 Ambulatory Treatment LY- CoV555 Monotherapy

Characteristic Ly-CoV555 (N=309) Placebo (N=143) Ly-CoV555 dosing: Age (years), median (range) 45 (18-86) 46 (18-77) ≥ 65, n (%) 33 (10.7) 20 (14.0) • 700 mg (N=101) Body-mass index (kg/m2), median 29.4 29.1 • 2800 mg (N=107) ≥ 30 to < 40, n/total (%) 112/304 (36.8) 56/139 (40.3) • 7000 mg (N=101) ≥ 40, no/total (%) 24/304 (7.9) 9/139 (6.5) Risk factors for severe COVID-19, n(%) 215 (69.6) 95 (66.4) Disease status, n(%) Risk factors for severe disease: Mild 232 (75.1) 113 (79.0) • Age ≥ 65 years Moderate 77 (24.9) 30 (21.0) • BMI ≥ 35 kg/m2 Days since symptom onset, median 4.0 4.0 • Prespecified coexisting illness Viral load (cycle threshold), mean 23.9 23.8

Chen P, et al. N Engl J Med. 2021;384(3):229-37. https://doi.org/10.1056/NEJMoa2029849 Ambulatory Treatment LY- CoV555 Monotherapy Primary Outcome: Mean change from baseline in viral load at day 11

Treatment Group Viral Load Change, mean Difference (95% CI) Placebo -3.47 LY-CoV555, 700 mg -3.67 -0.20 (-0.66 to 0.25) LY-CoV555, 2800 mg -4.00 -0.53 (-0.98 to -0.08) LY-CoV555, 7000 mg -3.38 0.09 (-0.37 to 0.55) Pooled LY-CoV555 doses -3.70 -0.22 (-0.60 to 0.15)

Chen P, et al. N Engl J Med. 2021;384(3):229-37. https://doi.org/10.1056/NEJMoa2029849 Ambulatory Treatment LY- CoV555 Monotherapy Secondary Outcome: Mean change from baseline in viral load at days 3 and 7

Day 3 Day 5

Treatment Group Viral Load Change, Difference Viral Load Change, Difference mean (95% CI) mean (95% CI) Placebo -0.85 -2.56 LY-CoV555, 700 mg -1.27 -0.42 (-0.89 to 0.06) -2.82 -0.25 (-0.73 to 0.23) LY-CoV555, 2800 mg -1.50 -0.64 (-1.11 to -0.17) -3.01 -0.45 (-0.92 to 0.03) LY-CoV555, 7000 mg -1.27 -0.42 (-0.90 to 0.06) -2.85 -0.28 (-0.77 to 0.20) Pooled LY-CoV555 doses -1.35 -0.49 (-0.87 to -0.11) -2.90 -0.33 (-0.72 to 0.06)

Chen P, et al. N Engl J Med. 2021;384(3):229-37. https://doi.org/10.1056/NEJMoa2029849 Ambulatory Treatment LY- CoV555 Monotherapy Secondary Outcomes: Hospitalizations, ED visits and Death • No deaths in any treatment group Treatment Group Hospitalization/ER Visits at Day 29* • Nearly all events were hospitalizations Placebo 9/143 (6.3) • 2 ED visits in placebo group • Post hoc analysis of high-risk patients LY-CoV555, 700 mg 1/101 (1.0) • LY-CoV555: 4/96 (4%) hospitalizations LY-CoV555, 2800 mg 2/107 (1.9) • Placebo: 7/48 (15%) hospitalizations LY-CoV555, 7000 mg 2/101 (2.0)

Pooled LY-CoV555 doses 5/309 (1.6)

*Placebo: 7 hospitalizations, 2 ER visits; LY-CoV555 all doses: 5 hospitalizations

Chen P, et al. N Engl J Med. 2021;384(3):229-37. https://doi.org/10.1056/NEJMoa2029849 Emergency Use Authorization for bamlanivimab 700mg IV. Center for Drug Evaluation and Research (CDER) Review. Available at: https://www.fda.gov/media/144118/download Ambulatory Treatment LY- CoV555 Monotherapy Secondary Outcomes: Symptom Score • Median time to symptom improvement • Pooled treatment: 6 days • Placebo: 8 days

Chen P, et al. N Engl J Med. 2021;384(3):229-37. https://doi.org/10.1056/NEJMoa2029849 US FDA: Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Bamlanivimab. Available at: https://www.fda.gov/media/143603/download Ambulatory Treatment LY- CoV555 Monotherapy Secondary Outcomes: Safety LY-CoV555 (N=309) Placebo 700 mg 2800 mg 7000 mg Pooled Doses (N=143) (N=101) (N=107) (N=101) (N=309) Serious adverse events, n(%) 0 0 0 0 1 (0.7) Adverse events Any 24 (23.8) 23 (21.5) 22 (21.8) 69 (22.3) 35 (24.5) Mild 16 (15.8) 18 (16.8) 10 (9.9) 44 (14.2) 18 (12.6) Moderate 7 (6.9) 3 (2.8) 8 (7.9) 18 (5.8) 16 (11.2) Severe 0 2 (1.9) 3 (3.0) 5 (1.6) 1 (0.7) Infusion-related reactions ------7 (2.3) 2 (1.4)

Chen P, et al. N Engl J Med. 2021;384(3):229-37. https://doi.org/10.1056/NEJMoa2029849 Ambulatory Treatment LY- CoV555 Monotherapy

Adverse Event 700 mg (N=101) 2800 mg (N=107) 7000 mg (N=101) Pooled Doses (N=309) Placebo (N=143) Nausea 3 (3.0) 4 (3.7) 5 (5.0) 12 (3.9) 5 (3.5) Diarrhea 1 (1.0) 2 (1.9) 7 (6.9) 10 (3.2) 7 (4.9) Dizziness 4 (4.0) 3 (2.8) 3 (3.0) 10 (3.2) 3 (2.1) Headache 3 (3.0) 2 (1.9) 0 5 (1.6) 3 (2.1) Pruritus 2 (2.0) 3 (2.8) 0 5 (1.6) 1 (0.7) Vomiting 1 (1.0) 3 (2.8) 1 (1.0) 5 (1.6) 4 (2.8) Chills 0 1 (0.9) 3 (3.0) 4 (1.3) 0 Fatigue 0 1 (0.9) 2 (2.0) 3 (1.0) 0 Hypertension 1 (1.0) 0 2 (2.0) 3 (1.0) 0 Lipase increased 1 (1.0) 0 2 (2.0) 3 (1.0) 0 Blood pressure increased 2 (2.0) 0 0 2 (0.6) 0

Chen P, et al. N Engl J Med. 2021;384(3):229-37. https://doi.org/10.1056/NEJMoa2029849 Emergency Use Approval • EUA granted for Bamlanivimab on November 9, 2020 for treatment of patients ≥ 12 years of age and ≥ 40 kg with mild/moderate COVID-19 at high risk of progressing to severe disease and/or hospitalization

High Risk Criteria ≥ 55 Years of Age and 12-17 Years of Age and • BMI ≥ 35 kg/m2 • Cardiovascular disease • BMI ≥ 85th percentile for age and gender • CKD • Hypertension • Sickle cell disease • Diabetes • COPD/other chronic • Congenital or acquired heart disease • Immunosuppressive disease respiratory disease • Neurodevelopmental disorders • Receiving immunosuppressive • Medical-related technology dependence treatment • Asthma, reactive airway or other • ≥ 65 years of age chronic respiratory disease requiring daily medication for control

• Administration • Administer within 10 days of symptom onset • Administer over 16-60 minutes depending on diluent volume • Observe patients for at least 1 hour after infusion is complete

US FDA: Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Bamlanivimab. Available at: https://www.fda.gov/media/143603/download Emergency Use Approval • Infectious Diseases Society of America (ISDA) Guidelines on the Treatment and Managements of Patients with COVID-19 • Among ambulatory patients with COVID-19, the IDSA guideline panel suggests against the routine use of Bamlanivimab

• National Institutes of Health (NIH) COVID-19 Treatment Guidelines • At this time, there are insufficient data to recommend either for or against the use of Bamlanivimab for the treatment of outpatients with mild to moderate COVID-19

LY-CoV555 2800 mg + LY-CoV016 2800 mg Characteristic Placebo (N=156) (N=112) Age (years), median (IQR) 44 (30-60) 46 (35-57) ≥ 65, n (%) 13 (12) 23 (15) Body-mass index (kg/m2), median (IQR) 27.2 (22.9-33.0) 29.2 (25.9-34.2) ≥ 30 to < 40, n/total (%) 33/109 (30) 63/152 (41) ≥ 40, no/total (%) 7/109 (6) 9/152 (6) Risk factors for severe COVID-19, n(%)* 67 (60) 105 (67) Mild disease, n(%) 92 (82) 125 (80) Moderate disease, n(%) 20 (18) 31 (20) Duration of symptoms, median (IQR) 4 (3-5) 4 (3-6) Viral load (cycle threshold), mean (SD) 22.7 (8.0) 23.8 (7.8) *Age ≥ 55, BMI ≥ 30 kg/m2, diabetes, chronic kidney disease, cardiovascular disease, chronic respiratory disease, immunosuppressive disease/treatment

Gottlieb RL, et al. JAMA. 2021. [Epub ahead of print]. https://doi.org/10.1001/jama.2021.0202 LY- CoV555 + LY- CoV016 Ambulatory Treatment Combination Therapy Primary Outcome: Mean change from baseline in viral load at day 11

Treatment Group n Viral Load Change, mean Difference (95% CI) Placebo 146 -3.80 LY-CoV555, 700 mg 100 -3.72 0.09 (-0.35 to 0.52) LY-CoV555, 2800 mg 103 -4.08 -0.27 (-0.71 to 0.16) LY-CoV555, 7000 mg 95 -3.49 0.31 (-0.13 to 0.76) LY-CoV555 + LY-CoV016 102 -4.37 -0.57 (-1.00 to -0.14)

Gottlieb RL, et al. JAMA. 2021. [Epub ahead of print]. https://doi.org/10.1001/jama.2021.0202 LY- CoV555 + LY- CoV016 Ambulatory Treatment Combination Therapy Secondary Outcomes: Viral Clearance and Symptom Burden • No significant differences between combination therapy group vs. placebo in any of the following on days 7, 11, 15 or 22: • Viral clearance (2 consecutive negative SARS-CoV-2 tests) • Symptom improvement • Symptom resolution (excluding loss of appetite & changes in taste/smell)

• Symptom scores improved vs. placebo on day 11 only

LY-CoV555 Monotherapy LY-CoV555 + LY-CoV016 Placebo 700 mg 2800 mg 7000 mg (N=109) (N=152) (N=101) (N=107) (N=101) Time to SARS-CoV-2 Clearance (days), median 25 23 25 21 24 Time to symptom improvement (days), median 6 6 6 6 8 Time to symptom resolution (days), median 8 8 9 8 9

LY-CoV555 Monotherapy LY-CoV555 + LY-CoV016 Placebo 700 mg 2800 mg 7000 mg (N=112) (N=156) (N=101) (N=107) (N=101) Hospitalization or ED visit at day 29, n(%)* 1 (1) 2 (1.9) 2 (2) 1 (0.9) 9 (5.8) P value (vs. placebo) 0.09 0.21 0.21 0.049 Hospitalization or ED visit at day 29 for 1/37 (2.7) 1/30 (3.3) 2/34 (5.9) 0/31 7/52 (13.5) patients ≥ 65 years or BMI ≥ 35 kg/m2, n(%) *12 hospitalizations, 3 ED visits

Gottlieb RL, et al. JAMA. 2021. [Epub ahead of print]. https://doi.org/10.1001/jama.2021.0202 LY- CoV555 + LY- CoV016 Ambulatory Treatment Combination Therapy Secondary Outcomes: Safety

LY-CoV555 LY-CoV555 + LY- Placebo CoV016 700 mg 2800 mg 7000 mg (N=156) (N=101) (N=107) (N=101) (N=112) Serious adverse events, n(%) 0 0 0 1 (0.9) 1 (0.6) Adverse events, n(%) Mild 17 (16.8) 18 (16.8) 10 (9.9) 15 (13.4) 21 (13.5) Moderate 7 (6.9) 5 (4.7) 7 (6.9) 3 (2.7) 18 (11.5) Severe 2 (2.0) 3 (2.8) 5 (5.0) 1 (0.9) 3 (1.9)

Infusion-related reactions, n(%) 6 (2.0) 2 (1.8) 1 (0.6)

Gottlieb RL, et al. JAMA. 2021. [Epub ahead of print]. https://doi.org/10.1001/jama.2021.0202 Ambulatory Treatment BLAZE-1 Phase 3 Higher Risk Population

Characteristic LY-COV555 2800 mg + LY-CoV016 2800 mg Placebo (N=517) (N=518) Hispanic/Latino 29% 30% African American 9% 8% Age (years), median 57 56 ≥ 65 years 32% 30% BMI (kg/m2), mean 34 33 Disease severity Mild 77% 78% Moderate 23% 22%

Eli Lilly. (2021). SARS-CoV-2 neutralizing antibody program update [Press release]. 26 January. Available at: https://investor.lilly.com/static-files/081a5ef7-f5d6-4acc-b0d2-7ae4daf9e953 US FDA: Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Bamlanivimab and Etesevimab. Available at: http://pi.lilly.com/eua/bam-and-ete-eua-factsheet-hcp.pdf LY- CoV555 + LY- CoV016 Ambulatory Treatment Combination Therapy (Prelim) BLAZE-1 Phase 3: High risk patients Primary Endpoint Other Endpoints • Similar rate of serious adverse events LY-CoV555 + LY-CoV016 Placebo P value (N=518) (N=517) • Significantly reduced mean viral load at day Hospitalization or death by 11 among combination therapy recipients 11 (2.1) 36 (7.0) 0.0004 any cause by day 29, n(%) • Significant difference seen as early as day 3 Death by any cause by • Significantly improved time to sustained 0 10 (1.9) < 0.001 day 29, n(%) symptom resolution (excluding mild cough or fatigue) among combination therapy recipients

Study Design Treatment Groups Outcomes • Phase 2, double-blind RCT • Bamlanivimab 700 mg + • Primary: Non-hospitalized adults Etesevimab 1400 mg IV x 1 • Viral load > 5.27 log10 on Day 7 • (+2 days) • ≥ 1 mild/moderate COVID- • Bamlanivimab 2800 mg + Etesevimab 2800 mg IV x 1 • Secondary: 19 symptom • Mean change in viral load from • 1st positive SARS-CoV-2 test • Bamlanivimab 700 mg IV x 1 baseline to Day 7 ≤ 72 hours from start of • Bamlanivimab 700 mg + • COVID-19 related hospitalization, ED visit, or infusion VIR-7831 500 mg IV x 1 death at day 29 • Exclusions: • Placebo • Symptom burden • Age ≥ 65 years • Safety • BMI ≥ 35 kg/m2

US FDA: Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Bamlanivimab and Etesevimab. Available at: http://pi.lilly.com/eua/bam-and-ete-eua-factsheet-hcp.pdf LY- CoV555 + LY- CoV016 Ambulatory Treatment Combination Therapy (Prelim) Baseline Characteristics Total Population Characteristic (N=515) Hispanic/Latino 29% • Bamlanivimab 700 mg + Etesevimab 1400 mg (N=158) African American 6% • Bamlanivimab 2800 mg + Etesevimab 2800 mg (N=101) Age (years), median 39 ≥ 65 years 1% • Bamlanivimab 700 mg (N=103) Disease severity • Placebo (N=153) Mild 84% Moderate 16% Viral load (CT), mean 25

US FDA: Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Bamlanivimab and Etesevimab. Available at: http://pi.lilly.com/eua/bam-and-ete-eua-factsheet-hcp.pdf LY- CoV555 + LY- CoV016 Ambulatory Treatment Combination Therapy (Prelim) Preliminary Results: SARS-CoV-2 viral load change from Bamlanivimab 700 mg Bamlanivimab 2800 mg Placebo baseline + Etesevimab 1400 mg + Etesevimab 2800 mg (N=135) (N=147) (N=99) Viral load > 5.27 on Day 7 21 (14) 10 (10) 42 (31) P value (vs. placebo) <0.001 <0.001

US FDA: Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Bamlanivimab and Etesevimab. Available at: http://pi.lilly.com/eua/bam-and-ete-eua-factsheet-hcp.pdf Emergency Use Approval • EUA granted for Bamlanivimab + Etesevimab on February 9, 2021 for treatment of patients ≥ 12 years of age and ≥ 40 kg with mild/moderate COVID-19 at high risk of progressing to severe disease and/or hospitalization

US FDA: Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Bamlanivimab. Available at: https://www.fda.gov/media/143603/download Emergency Use Approval • Dosing • Bamlanivimab 700 mg + Etesevimab 1400 mg IV x 1 • Must combine 1 vial Bamlanivimab + 2 vials Etesevimab • No dosage adjustments for any specific populations

• Administration • Administer within 10 days of symptom onset • Infusion duration 21-70 minutes depending on patient weight and diluent volume • Observe patients for at least 1 hour after infusion is complete

• National Institutes of Health (NIH) COVID-19 Treatment Guidelines • The Panel recommends the use of Bamlanivimab 700 mg plus Etesevimab 1400 mg for the treatment of outpatients with mild to moderate COVID-19 who are at high risk of clinical progression as defined by the EUA criteria.

Study Design Treatment Groups Outcomes • Resident/staff of nursing • Bamlanivimab 4200 mg IV x 1 • Primary home with ≥ 1 confirmed case • Placebo • Cumulative incidence of COVID-19 of SARS-CoV-2 detection ≤ 7 (detection of SARS-CoV-2 viral + mild or worse disease severity days prior to randomization within 21 days of detection) • No history of confirmed • Secondary COVID-19, asymptomatic • Cumulative incidence of SARS-CoV- infection, or receipt of 2 infection + moderate or worse convalescent plasma or SARS- disease severity within 21 days of CoV-2 vaccine detection • Safety

Eli Lilly. (2021). SARS-CoV-2 neutralizing antibody program update. 26 January. Available at: https://investor.lilly.com/static-files/081a5ef7-f5d6-4acc-b0d2-7ae4daf9e953 LY- CoV555 Monotherapy Ambulatory Prophylaxis (Prelim) Preliminary Results:

Bamlanivimab 700 mg Placebo P value (N=160) (N=139) Symptomatic COVID-19, n(%) 14 (8.8) 31 (22.3) 0.00026 Deaths due to COVID-19, n(%) 0 4 (2.9)

Eli Lilly. (2021). SARS-CoV-2 neutralizing antibody program update. 26 January. Available at: https://investor.lilly.com/static-files/081a5ef7-f5d6-4acc-b0d2-7ae4daf9e953 Emergency Use Approval • EUA request for Bamlanivimab as post-exposure prophylaxis will be submitted

Study Design Treatment Groups • Phase 3, double-blind RCT • LY-CoV555 7000 mg IV x 1 • Hospitalized adults • Placebo • + SARS-CoV-2 test ≤ 3 days prior to randomization (or progressive disease with positive test > 3 days prior) Outcomes • COVID-19 symptoms ≤ 12 days • Primary: sustained recovery • None of the following: • Discharge to home • Stroke • Remain at home for ≥ 14 days • Meningitis, encephalitis, myelitis • Secondary: all-cause mortality • MI, myocarditis, pericarditis, CHF NYHA class III/IV • Futility assessment • Arterial/deep venous thrombosis or pulmonary embolism • “Pulmonary” outcome: oxygen requirements • End organ failure • “Pulmonary-plus” outcome: extrapulmonary manifestations

Lundgren JD, et al. N Engl J Med. 2020. [Epub ahead of print]. https://doi.org/10.1056/NEJMoa2033130 Inpatient Treatment ACTIV-3

Category Pulmonary Ordinal Outcomes Pulmonary-Plus Ordinal Outcomes 1 Can independently undertake usual• activitiesLY-CoV555 with minimal/no 7000 mg symptoms x 1

2 Symptomatic, currently unable to independently undertake usual• activitiesPlacebo but no need of supplemental O2 (or not above premorbid requirements)

3 Supplemental O2 <4 L/min (or < 4 L/min above premorbid requirements)

4 Supplemental O2 ≥ 4 L/min (or ≥4 L/min Supplemental O2 requirement ≥ 4 L/min (or ≥4 L/min above premorbid requirements), above premorbid requirements) stroke (NIHSS ≤ 14), meningitis, encephalitis, myelitis, MI, myocarditis, pericarditis, CHF NYHA class III or IV, arterial or deep venous thromboembolic event

5 Non-invasive ventilation or high-flow O2 Non-invasive ventilation or high-flow O2, or s/sx of acute stroke (NIHSS > 14) 6 Invasive ventilation, ECMO, mechanical Invasive ventilation, ECMO, mechanical circulatory support, vasopressor therapy, or circulatory support, or new receipt of renal new receipt of renal replacement therapy replacement therapy 7 Death

Lundgren JD, et al. N Engl J Med. 2020. [Epub ahead of print]. https://doi.org/10.1056/NEJMoa2033130 Inpatient Treatment LY- CoV555 Monotherapy

Characteristic Ly-CoV555 (N=163) Placebo (N=151) Age (years), median (IQR) 63 (50-72) 59 (48-71) Race or ethnic group, n(%) Hispanic 41 (25) 33 (22) Black 33 (20) 34 (23) Body mass index, n(%) ≥ 30 81 (50) 83 (55) ≥ 40 20 (12) 22 (15) Days since symptom onset, median (IQR) 7 (5-9) 8 (5-9) Oxygen requirement, n(%) None 44 (27) 42 (28) <4 L/min 60 (37) 57 (38) ≥4 L/min 29 (18) 34 (23) Non-invasive/high-flow device 30 (18) 18 (12) Any coexisting illness, n(%) 117 (72) 98 (65)

Lundgren JD, et al. N Engl J Med. 2020. [Epub ahead of print]. https://doi.org/10.1056/NEJMoa2033130 Inpatient Treatment LY- CoV555 Monotherapy • Remdesivir • 40% receiving treatment at the time of randomization • 95% receiving treatment before or on the day of randomization

• Glucocorticoids • 49% receiving treatment at the time of randomization

Lundgren JD, et al. N Engl J Med. 2020. [Epub ahead of print]. https://doi.org/10.1056/NEJMoa2033130 Inpatient Treatment LY- CoV555 Monotherapy Futility Analysis: Pulmonary Ordinal Outcome

Lundgren JD, et al. N Engl J Med. 2020. [Epub ahead of print]. https://doi.org/10.1056/NEJMoa2033130 Inpatient Treatment LY- CoV555 Monotherapy Pulmonary Ordinal Outcome at Day 5 by Baseline Category 100%

80% Category 7 Category 6 60% Category 5 Category 4 40% Category 3 Category 2 20% Category 1

0% LY- Placebo LY- Placebo LY- Placebo LY- Placebo CoV555 CoV555 CoV555 CoV555 2 3 4 5 Baseline Pulmonary Ordinal Outcome Category Lundgren JD, et al. N Engl J Med. 2020. [Epub ahead of print]. https://doi.org/10.1056/NEJMoa2033130 Inpatient Treatment LY- CoV555 Monotherapy Additional Efficacy and Safety Outcomes: Assessed through Oct. 26

LY-CoV555 Placebo (N=163) (N=151) Sustained recovery*, n(%) 71/87 (82) 64/81 (79) LY-CoV555 Placebo

Hospital discharge, n(%) 143/163 (88) 136/151 (90) Death, n(%) 1 (0.6) 0 Infusion reaction, n(%) 23 (14) 14 (9) SAE, n(%) 4 (2.5) 2 (1.3) Grade 3 or 4 event, n(%) 30 (18.4) 21 (13.9) Composite safety outcome†, n(%) 38 (23) 30 (20) Death, n(%) 9 (6) 5 (3) *assessed among patients followed for ≥ 28 days or died within 28 days †death, serious adverse events (SAE), or clinical grade 3 or 4 adverse events through day 5

Lundgren JD, et al. N Engl J Med. 2020. [Epub ahead of print]. https://doi.org/10.1056/NEJMoa2033130 Inpatient Treatment LY- CoV555 Monotherapy Time to Sustained Recovery and Hospital Discharge

Lundgren JD, et al. N Engl J Med. 2020. [Epub ahead of print]. https://doi.org/10.1056/NEJMoa2033130 Summary LY- CoV555 and LY- CoV016 • Bamlanivimab + Etesevimab • Significantly reduces viral load from baseline vs. placebo in ambulatory patients • Minimal impact on viral clearance and symptom improvement • May prevent hospitalizations/ED visits, especially in high-risk ambulatory patients • Awaiting full phase 3 results from BLAZE-1

• Bamlanivimab • No increased reduction in viral load from baseline in ambulatory patients • No impact on clinical improvement vs. placebo in patients hospitalized for COVID-19 • May prevent acquisition of symptomatic COVID-19 infection in nursing home staff/residents • Awaiting full results from BLAZE-2 Regeneron: Casirivimab + Imdevimab Alternate Names: REGN10933 + REGN10987 REGN-CoV2 REGN-COV2 – In vitro Activity • 200 neutralizing mAbs identified  4 finalists selected

Neutralization Potency Antibody Effector Functions

*Antibody-dependent cellular phagocytosis

Hansen J, et al. Science. 2020;369:1010-4. https://doi.org/10.1126/science.abd0827 REGN-COV2 – In vitro Activity

Baum A, et al. Science. 2020;369:1014-8. https://doi.org/10.1126/science.abd0831 In vivo Animal Data Rhesus Macaque

Prophylaxis Treatment Study 1 Study 2 Antibody administered 1 day Methods Antibody administered 3 days prior to viral challenge after viral challenge Viral Inoculum 1.0 x 105 PFU 1.05 x 106 PFU 1.05 x 106 PFU 0.3 mg/kg (N=4) 25 mg/kg (N=4) 50 mg/kg (N=6) Antibody Doses 50 mg/kg (N=4) 150 mg/kg (N=4) Placebo (N=6) Placebo (N=4) Placebo (N=4) Nasopharyngeal swab Nasopharyngeal swab Nasopharyngeal swab Sample Types BAL Oral swab Oral swab Outcomes Change in viral load (gRNA and sgRNA)

Baum A, et al. Science. 2020;eabe2402. https://doi.org/10.1126/science.abe2402 In vivo Animal Data Rhesus Macaque Key Findings - Prophylaxis Key Findings - Treatment • Increased rates of gRNA clearance, near complete • Similarly increased viral clearance (gRNA and sgRNA) ablation of sgRNA among animals receiving 50 mg/kg among animals receiving either 25 mg/kg or 150 mg/kg • Viral clearance rates similar between NP swab and BAL fluid samples; more rapid clearance noted on oral swab samples

Baum A, et al. Science. 2020;eabe2402. https://doi.org/10.1126/science.abe2402 In vivo Animal Data Golden Hamster

Prophylaxis Treatment Antibody administered 1 day Methods Antibody administered 2 days prior to viral challenge after viral challenge Viral Inoculum 2.3 x 104 PFU 50 mg/kg (N=5) 5 mg/kg (N=5) Antibody Doses 0.5 mg/kg (N=5) Placebo (N=5) Sample Types Lung tissue N/A Body weight change Outcomes Change in viral load (gRNA and sgRNA) Body weight change Area of lung exhibiting pathology typical of pneumonia

Baum A, et al. Science. 2020;eabe2402. https://doi.org/10.1126/science.abe2402 In vivo Animal Data Golden Hamster Key Findings Weight Loss • Decreased weight loss among all groups Prophylaxis Treatment receiving prophylaxis • Treatment with higher doses prevented weight loss • Viral load not significantly impacted by prophylaxis Viral Load on Day 7 (Prophylaxis) Affected Lung Genomic RNA Subgenomic RNA • Significantly less lung affected in animals receiving prophylactic antibodies

Baum A, et al. Science. 2020;eabe2402. https://doi.org/10.1126/science.abe2402 Clinical Trials

NCT Number Patient Population Treatment Groups Status REGN-COV2 2.4 g IV x 1 Recruiting – data NCT04425629 Treatment of outpatients with mild to moderate COVID-19 illness REGN-COV2 8 g x 1 available Placebo REGN-COV2 2.4 g IV x 1 Recruiting – press NCT04426695 Treatment of hospitalized patients with COVID-19 illness REGN-COV2 8 g IV x 1 release data available Placebo NCT04381936 REGN-COV2 8 g IV x 1 Treatment of hospitalized patients with COVID-19 illness Recruiting RECOVERY Standard care REGN-COV2 SubQ x 1 Prevention of COVID-19 illness in household contacts of individuals Recruiting – press NCT04452318 REGN-COV2 IM x 1 infected with SARS-CoV-2 release data available Placebo REGN-COV2 IV x 1 (4 different doses) Treatment of low-risk outpatients with asymptomatic, mild, or NCT04666441 REGN-COV2 SubQ x 1 (2 different doses) Recruiting moderate COVID-19 illness Placebo

Source: https://clinicaltrials.gov REGN- COV2 Combination Ambulatory Treatment Therapy Patient Population Treatment Groups Outcomes • Non-hospitalized adults • 2.4 grams IV x 1 • Virologic: • Symptom onset ≤ 7 days • 8.0 grams IV x 1 • Serum Ab-negative patients from randomization • Time-weighted average • Placebo change from baseline in • SARS-CoV-2 confirmed by viral load through day 7 molecular testing ≤ 72 • Clinical: hours from randomization • Serum Ab-negative and • Not on any putative overall patient populations COVID-19 therapies • Proportion of patients with ≥ 1 COVID-19-related medically-attended visit through day 29

Weinreich DM, et al. N Engl J Med. 2021;384(3):238-51. https://doi.org/10.1056/NEJMoa2035002 REGN- COV2 Combination Ambulatory Treatment Therapy Baseline Demographics Placebo REGN-COV2 2.4g REGN-COV2 8.0g Total (N=93) (N=92) (N=90) (N=275) Age (years), median (IQR) 45 (34-54) 43 (33.5-51) 44 (36-53) 44 (35-52) Male sex, n (%) 50 (54) 46 (50) 38 (42) 134 (49) Hispanic or Latino, n (%) 46 (49) 52 (57) 55 (61) 153 (56) Race, n (%) White 72 (77) 74 (80) 78 (87) 224 (81) Black/African American 14 (15) 15 (16) 6 (7) 35 (13) BMI > 30 kg/m2, n (%) 34 (37) 39 (42) 42 (47) 115 (42) ≥ 1 Risk factor for hospitalization*, n (%) 58 (62) 57 (62) 61 (68) 176 (64) *Age > 50 years, obesity, cardiovascular disease, chronic lung disease, chronic metabolic disease, chronic kidney disease, chronic liver disease, immunocompromise

Weinreich DM, et al. N Engl J Med. 2021;384(3):238-51. https://doi.org/10.1056/NEJMoa2035002 REGN- COV2 Combination Ambulatory Treatment Therapy Baseline Viral Load

Placebo REGN-COV2 2.4g REGN-COV2 8.0g Total Baseline serology status: negative N = 31 N = 37 N = 36 N = 104 Viral load, median copies/mL 14 x 106 2.24 x 106 32.05 x 106 15 x 106 Baseline serology status: positive N = 47 N = 36 N = 37 N = 120 Viral load, median copies/mL 4,790 4,460 1,740 3,105 Baseline serology status: unknown N = 13 N = 11 N = 10 N = 34 Viral load, median copies/mL 82,800* 937,000† 2,320,000 145,500 Ranges for all viral loads were 1:71x106 copies/mL with the following exceptions: *Range 357:25.6x106 copies/mL †Range 2200:71x106 copies/mL

Weinreich DM, et al. N Engl J Med. 2021;384(3):238-51. https://doi.org/10.1056/NEJMoa2035002 REGN- COV2 Combination Ambulatory Treatment Therapy Results: Key virologic end point Placebo REGN-COV2 2.4g REGN-COV2 8.0g MFAS Sero(-) Sero(+) MFAS Sero(-) Sero(+) MFAS Sero(-) Sero(+) (N=78) (N=28) (N=37) (N=70) (N=34) (N=27) (N=73) (N=35) (N=29) Time-weighted average change in viral load through day 7 (log10 -1.34±0.13 -1.37±0.20 -1.24±0.16 -1.60±0.14 -1.89±0.18 -1.24±0.19 -1.90±0.14 -1.96±0.18 -1.63±0.20 copies/mL), mean (SE) Difference vs. placebo (log 10 -0.25±0.18 -0.52±0.26 0.00±0.24 -0.56±0.18 -0.60±0.26 -0.39±0.25 copies/mL)

Weinreich DM, et al. N Engl J Med. 2021;384(3):238-51. https://doi.org/10.1056/NEJMoa2035002 REGN- COV2 Combination Ambulatory Treatment Therapy • Greater viral load reduction among patients with higher baseline viral load

Weinreich DM, et al. N Engl J Med. 2021;384(3):238-51. https://doi.org/10.1056/NEJMoa2035002 REGN- COV2 Combination Ambulatory Treatment Therapy Results: Key clinical end point

Placebo REGN-COV2 2.4g REGN-COV2 8.0g FAS Sero(-) Sero(+) FAS Sero(-) Sero(+) FAS Sero(-) Sero(+) (N=93) (N=33) (N=47) (N=92) (N=41) (N=37) (N=90) (N=39) (N=39)

Medically attended visits, n (%) 6 (6) 5 (15) 1 (2) 3 (3) 2 (5) 1 (3) 3 (3) 3 (8) 0

Weinreich DM, et al. N Engl J Med. 2021;384(3):238-51. https://doi.org/10.1056/NEJMoa2035002 REGN- COV2 Combination Ambulatory Treatment Therapy Safety Placebo REGN-COV2 2.4g REGN-COV2 8.0g (N=93) (N=88) (N=88) Serious adverse event 2 (2) 1 (1) 0 Infusion-related reactions Grade ≥ 2 thru Day 4 1 (1) 0 2 (2) Hypersensitivity reactions Grade ≥ 2 thru Day 29 2 (2) 0 1 (1) Event leading to death 0 0 0 Event leading to infusion interruption 1 (1) 0 1 (1)

Weinreich DM, et al. N Engl J Med. 2021;384(3):238-51. https://doi.org/10.1056/NEJMoa2035002 Ambulatory Treatment EUA Data

• Primary Outcome: time-weighted average change in viral load through day 7

Patient Population TWA Change in Viral Load vs. Placebo (log10 copies/mL) EUA Interim Data – NEJM (N=665) (N=275) Modified full analysis set -0.36 -0.41 High viral load -0.78 -- Seronegative -0.69 -0.56

US FDA: Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Casirivimab and Imdevimab. Available at: https://www.fda.gov/media/143892/download Ambulatory Treatment EUA Data • Secondary Outcomes:

Placebo REGN-CoV2 2.4g REGN-CoV2 8.0g Combined REGN-Cov2 Hospitalization/ER visits within 28 days, n/N (%) 10/231 (4) 4/215 (2) 4/219 (2) 8/434 (2) High risk patients*† 7/78 (9) 2/70 (3) 2/81 (2) 4/151 (3) Time to symptom improvement, median (days) 6 -- -- 5 *High risk = patients meeting EUA criteria for use †Placebo: 3 hospitalizations, 4 ER visits; REGN 2.4g & 8g: 1 hospitalization, 1 ER visit each

US FDA: Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Casirivimab and Imdevimab. Available at: https://www.fda.gov/media/143892/download Emergency Use Authorization for casirivimab and imdevimab. Center for Drug Evaluation and Research (CDER) Review. Available at: https://www.fda.gov/media/144468/download Emergency Use Approval • EUA granted November 21, 2020 for treatment of patients ≥ 12 years of age and ≥ 40 kg with mild/moderate COVID-19 at high risk of progressing to severe disease and/or hospitalization

• Administration • Administer within 10 days of symptom onset • Administer over at least 60 minutes • Observe patients for at least 1 hour after infusion is complete

US FDA: Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Casirivimab and Imdevimab. Available at: https://www.fda.gov/media/143892/download Emergency Use Approval • Infectious Diseases Society of America (ISDA) Guidelines on the Treatment and Managements of Patients with COVID-19 • Among ambulatory patients with COVID-19, the IDSA guideline panel suggests against the routine use of Casirivimab/Imdevimab

• National Institutes of Health (NIH) COVID-19 Treatment Guidelines • At this time, there are insufficient data to recommend either for or against the use of Casirivimab plus Imdevimab for the treatment of outpatients with mild to moderate COVID-19

Bhimraj A, at al. Treatment and management of patients with COVID-19. Infectious Diseases Society of America. Available at: http://www.idsociety.org/COVID19guidelines. Accessed [1/12/21] COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at: https://www.covid19treatmentguidelines.nih.gov. Accessed [1/12/21] REGN- COV2 Combination Inpatient Treatment Therapy (Prelim Data) Patient Population Available Results (Seronegative Population) • Futility analysis: PASSED • Hospitalized adults on low-flow O2 • Receipt of REGN-COV2 ↓ risk of death/mechanical • 217 seronegative ventilation (HR: 0.78; 80% CI: 0.51-1.2) • 270 seropositive • Starting 1 week post-treatment, risk of death/mechanical • 67% received remdesivir ventilation reduced by half • 74% received corticosteroids • Change in TWA daily viral load: • Through day 7: -0.54 log10 copies/mL Treatment Groups • Through day 11: -0.63 log10 copies/mL • 2.4 grams IV x 1 • On day 5 vs. Placebo: -1.1 log10 copies/mL • 8.0 grams IV x 1 • Adverse events in overall population: • Placebo • 2.4g dose: 20% (Infusion reactions: 0.9%) • 8.0g dose: 21% (Infusion reactions: 2.7%) • Placebo: 24% (Infusion reactions: 1.4%)

Regeneron. (2020). REGN-COV2 antibody cocktail program update [Press release]. 29 December. Available at: https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-encouraging-initial-data-covid-19-antibody REGN- COV2 Combination Ambulatory Prophylaxis Therapy (Prelim Data) Patient Population Available Results • Asymptomatic adult and pediatric patients REGN-COV2 Placebo (N=186) (N=223) • Household exposure to SARS-CoV-2 positive individual within 96h of Total infection, n(%) 10 (5.4) 23 (10.3) positive test Symptomatic infection, n(%) 0 8 (3.6) • Resides in same household as index case until study day 29 • Adverse events more frequent in placebo group (18%) vs. REGN-COV2 treated (12%) Treatment Groups • Injection site reactions occurred in 2% of patients in both groups • 1200 mg SubQ x 1 • 1 death + 1 hospitalization in placebo group vs. 0 deaths/hospitalizations in treatment group • Placebo

Regeneron. (2021). REGN-COV2 antibody cocktail program update [Press release]. 26 January. Available at: https://investor.regeneron.com/news-releases/news-release-details/regeneron-reports-positive-interim-data-regen-covtm-antibody Summary REGN- COV2 • Casirivimab + Imdevimab • Greatest viral load changes observed in seronegative patients or patients with high baseline viral load (> 106 copies/mL) • Minimal impact on symptom improvement • May prevent hospitalizations/ER visits, especially in high-risk ambulatory patients • May decrease progression to mechanical ventilation or death in seronegative patients hospitalized with COVID-19 on low-flow supplemental oxygen • Awaiting full clinical trial results • May decrease risk of infection in household contacts of persons infected with COVID-19 • Awaiting full clinical trial results Monoclonal Antibody Efficacy Against Select SARS-CoV-2 Variants SARS-CoV-2 Variants

Variant First Detected Key Mutations in the Receptor Binding Domain (RBD) B.1.1.7 United Kingdom N501Y N501Y B.1.351 South Africa E484K K417N N501Y P.1 Japan/Brazil E484K K417N/T B.1.429 California L452R

CDC - SARS-CoV-2 Variants. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant- surveillance/variant-info.html. February 25, 2021 Zhang W, et al. JAMA. 2021. [Epub ahead of print]. http://doi.org/10.1001/jama.2021.1612 Escape Mutant Impact LY- CoV555 & LY- CoV016

Viral Mutation Mapping Fold Change in IC50 from Wild Type

(Bamlanivimab) B.1.1.7 LY- LY- B.1.351 LY- LY- (UK) CoV555 CoV016 (SA) CoV555 CoV016 69-70del 1.1 1.5 L18F 1.0 1.3 144del 1.1 1.2 D80A 1.5 1.4 (CB6/Etesevimab) N501Y -1.0 -2.6 D215G 1.5 1.6 A570D 1.7 4.6 242-244del -1.1 -1.1 P681H 2.3 1.1 R246I 1.4 1.7 T716I 3.5 3.4 K417N 8.4 <-1000 S982A -2.0 -3.6 E484K <-1000 -3.5 D1118H 1.0 1.4 N501Y -1.0 -2.6 A701V 2.0 1.6

Starr TN, et al. bioRxiv [Preprint]. 2021. https://doi.org/10.1101/2021.02.17.431683 Wang P, et al. bioRxiv [Preprint]. 2021. https://doi.org/10.1101/2021.01.25.428137 Escape Mutant Impact LY- CoV555 & LY- CoV016

LY-CoV555 CB6/LY-CoV016 Combination

Wang P, et al. bioRxiv [Preprint]. 2021. https://doi.org/10.1101/2021.01.25.428137 Hoffman M, et al. bioRxiv [Preprint). 2021. https://doi.org/10.1101/2021.02.11.430787 Escape Mutant Impact REGN10933 & REGN10987

Viral Mutation Mapping Fold Change in IC50 from Wild Type (Casirivimab) B.1.1.7 REGN- REGN- B.1.351 REGN- REGN- (UK) 10933 10987 (SA) 10933 10987 69-70del 1.3 1.2 L18F 1.4 -1.8 144del 1.3 -1.4 D80A 1.4 -2.2 (Imdevimab) N501Y -1.4 1.3 D215G 1.5 -2.1 A570D 4.7 -1.6 242-244del 1.0 -3.2 P681H 1.6 -1.9 R246I 2.2 -2.1 T716I 3.6 -1.6 K417N -13.1 -1.2 S982A -2.3 -1.2 E484K -10.5 -1.1 D1118H -1.3 -1.7 N501Y -1.4 1.3 A701V 2.3 -2.6

Starr TN, et al. Science. 2021. [Epub ahead of print]. https://doi.org/10.1126/science.abf9302 Wang P, et al. bioRxiv [Preprint]. 2021. https://doi.org/10.1101/2021.01.25.428137 Escape Mutant Impact LY- CoV555 & LY- CoV016

REGN10933 REGN10987 Combination

Wang P, et al. bioRxiv [Preprint]. 2021. https://doi.org/10.1101/2021.01.25.428137 Hoffman M, et al. bioRxiv [Preprint). 2021. https://doi.org/10.1101/2021.02.11.430787 Escape Mutant Impact Summary

Efficacy Retained? Variant First Detected Key Mutations LY-CoV555 LY-CoV555 + REGN10933 + Monotherapy LY-CoV016 REGN10987 B.1.1.7 United Kingdom N501Y Y Y Y N501Y B.1.351 South Africa E484K N N Y K417N N501Y B.1.1.248 Japan/Brazil E484K N N Y K417N/T B.1.427/B.1.429 California L452R Unknown Unknown Y Additional mAb Under Investigation

Name Developer Study Design Phase 2/3 – outpatient treatment Sotrovimab (VIR-7831) Vir biotechnology/GSK Phase 3 – inpatient treatment Regdanvimab (CT-P59) Celltrion Phase 2/3 – outpatient treatment Phase 3 – pre/post-exposure prophylaxis Tixagevimab + Cilgavimab AstraZeneca/Vanderbilt University Medical Phase 3 – inpatient treatment (AZD8895 + AZD1061) Center/DARPA/BARDA Phase 3 – outpatient treatment TY027 Tychan Phase 3 – inpatient treatment BRII-196 + BRII-198 Brii Biosciences/NIAID Phase 3 – inpatient treatment

Yang L, et al. Antibody Therapeutics. 2020;3:205-12. https://doi.org/10.1093/abt/tbaa020 Monoclonal Antibodies

A Review of Pertinent Drug Information for SARS-CoV-2

Jessica Ortwine, PharmD, BCIDP Clinical Pharmacy Specialist, Parkland Health & Hospital System [email protected] @jkortwine

Data as of February 25, 2021